A fusion protein of hepatocyte growth factor enhances reconstruction of myocardium in a cardiac patch derived from porcine urinary bladder matrix.

Abstract

We sought to promote myocardial repair using urinary bladder matrix incorporated with a fusion protein that combined hepatocyte growth factor and fibronectin collagen-binding domain in a porcine model. Collagen-binding domain acted as an intermediary to promote hepatocyte growth factor binding and enhance hepatocyte growth factor stability within urinary bladder matrix. Urinary bladder matrix incorporated with collagen-binding domain and hepatocyte growth factor was implanted into the porcine right ventricular wall (F group) to repair a surgically created defect. Untreated urinary bladder matrix patches (U group) and Dacron patches (D group) served as controls (N = 5/group). Electromechanical mapping was performed 60 days after surgery. Linear local shortening was used to assess regional contractility, and electrical activity was recorded. Linear local shortening was significantly improved in the F group compared with controls (F: 0.51% +/- 1.57% [P < .05], U: -1.06% +/- 1.84%, D: -2.72% +/- 2.59%), whereas it was inferior to the normal myocardium (13.7% +/- 4.3%; P < .05). Mean electrical activity was 1.49 +/- 0.82 mV in the F group, which was statistically greater than in the control groups (U: 0.93 +/- 0.71 mV; D: 0.30 +/- 0.22 mV; P < .05) and less than the normal myocardium (8.24 +/- 2.49 mV; P < .05). Histologic examination showed predominant alpha-smooth muscle actin positive cells with the F group showing the thickest layer and the D group showing the thinnest layer, with an endocardial endothelial monolayer. Scattered isolated islands of alpha-actinin positive cells were observed only in the F group, but not in the controls, suggesting the presence of cardiomyocytes. The collagen-binding domain/hepatocyte growth factor/urinary bladder matrix patch demonstrated increased contractility and electrical activity compared with urinary bladder matrix alone or Dacron and facilitated a homogeneous repopulation of host cells. Urinary bladder matrix incorporated with collagen-binding domain and hepatocyte growth factor may contribute to constructive myocardial remodeling.